In response to swelling, cells recover their initial volume by releasing intracellular solutes via volume-sensitive pathways. There is increasing evidence that structurally dissimilar organic osmolytes (amino acids, polyols, methyl amines), which are lost from cells in response to swelling, share a single pathway having the characteristics of an anion channel. However, the molecular identity of this pathway remains to be established. It has been suggested that the erythrocyte anion exchanger (AE1) or some AE1-related proteins could be involved. A direct evaluation of this possibility has been made by comparing the functional properties of two AE1s when expressed in Xenopus laevis oocytes: tAE1 is from a fish erythrocyte which releases taurine when swollen, and mAE1 is from a mammalian erythrocyte which does not regulate its volume when swollen. While mAE1 performs exclusively Cl-/Cl- exchange, tAE1 behaves as a bifunctional protein with both anion exchange and Cl-/taurine channel functions. Construction of diverse tAE1/mAE1 chimaeras allows the identification of protein domains associated with this channel activity. Thus, some AE1 isoforms could act as a swelling-activated osmolyte channel, a result having a potentially important implication in malaria. This review also discusses the possibility that several different proteins might function as swelling-activated osmolyte channels.

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